ABSTRACT Ventilator associated pneumonia (VAP) is one of the most costly and deadly nosocomial infections. Over 250,000 cases of VAP occur per year resulting in over 36,000 deaths and a cumulative annual cost to the US Healthcare system over 3 Billion. Endotracheal tubes (ETT) are inserted into the trachea to allow mechanical ventilation. They are a critical part of the ventilator circuit but also provide a conduit for transmission of bacteria to the lungs. Biofilms form rapidly on ETTs and are thought to play a key role in VAP development as well as the antibiotic resistance and persistence commonly seen with VAP. The goal of this project is to develop an innovative antimicrobial endotracheal tube (ETT) that is effective against biofilm producing pathogens associated with VAP. The proposed ETT will be coated with a novel polymer formulation of an engineered cationic antimicrobial peptide (eCAP) previously shown to be effective against drug resistant bacteria common to VAP. The polymer coating will provide controlled eCAP release and protection of the peptide until release. It will also will provide a hydrophilic, biocompatible interface resistant to fouling. The scope of work covers development of the coating formulation and application to ETTs with an evaluation of coating stability and ETT cuff compliance. eCAP release rates and stability in artificial saliva will be measured by RP-HPLC. Feasibility will be demonstrated using Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus, which are two of the most common causative organisms in VAP. The plan includes studies designed to show prevention of biofilm formation on coated ETTs. The plan also employs an in vitro model that is designed to evaluate the roles that both ETT balloon compliance and bactericidal effect play in preventing bacteria transfer from the throat to the lungs. Finally, cytotoxicity against tracheal epithelial cells will be assessed. If successful, the product is expected to have a significant and sustained impact on reducing morbidity and mortality associated with VAP.